FGF-2 for Ear Drum Perforation

Overseen By Ashley Feng

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Radiation, Corticosteroids, Immunosuppressants, Chemotherapy

Disqualifiers: Otitis media, Immunosuppressed, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests FGF-2, a protein that helps heal tissues, on patients with chronic ear drum holes that don't heal naturally. FGF-2 works by promoting new cell growth and tissue repair to close the holes. FGF-2 has been widely used for burn treatment and wound healing due to its ability to stimulate cell growth and repair.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop certain medications. The trial excludes participants who are taking radiation therapy, corticosteroids, immunosuppressive agents, chemotherapy, or systemic antibiotics.

Will I have to stop taking my current medications?

The trial requires that participants not be taking certain medications, such as radiation therapy, corticosteroids, immunosuppressive agents, chemotherapy, or systemic antibiotics. If you are on any of these, you would need to stop them to participate in the trial.

What data supports the idea that FGF-2 for Ear Drum Perforation is an effective treatment?

The available research shows that FGF-2 is effective in treating ear drum perforations. Studies have shown that FGF-2 helps heal chronic and traumatic perforations of the ear drum. However, one study found that another treatment, HB-EGF, was more effective than FGF-2 in an animal model. This suggests that while FGF-2 works, there might be even better options available. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment FGF-2 for ear drum perforation?

Research shows that fibroblast growth factor-2 (FGF-2) can help heal chronic and traumatic ear drum perforations, making it more effective than doing nothing or using a placebo. ^{1 2 3 4 5}

What safety data is available for FGF-2 in treating ear drum perforations?

The safety data for FGF-2 in treating tympanic membrane perforations includes findings from various studies. In a study on rats, a higher dose of FGF led to a high rate of myringitis, indicating potential safety concerns at higher concentrations. However, at a dose of 200 ng, no significant difference in safety was observed between the FGF and placebo groups. Systematic reviews and studies have focused on the effectiveness and safety of FGF-2, but specific safety outcomes are not detailed in the abstracts provided. ^{1 2 6 7 8}

Is FGF-2 safe for treating ear drum perforations?

FGF-2 has been used in studies to help heal ear drum perforations, and while it generally promotes healing, higher doses have been linked to myringitis (inflammation of the ear drum). At lower doses, it appears to be safe, with no significant difference in side effects compared to a placebo. ^{1 2 6 7 8}

Is FGF-2 a promising drug for healing ear drum perforations?

Yes, FGF-2 is a promising drug for healing ear drum perforations. Studies show that it helps the ear drum heal faster compared to not using it, making it a valuable option for treating these injuries. ^{1 2 6 8 9}

How is the treatment FGF-2 unique for ear drum perforation?

FGF-2 is unique because it is applied topically (directly on the ear) and works by promoting cell growth to help heal the ear drum faster, unlike other treatments that may not specifically target cell regeneration. ^{1 2 6 8 9}

Research Team

David Friedmann, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

Adults over 18 with chronic ear drum perforations lasting at least 6 months can join. They must not be pregnant, agree to birth control use, and have no severe diabetes, ear shape abnormalities, active middle ear infections or recent substance abuse. Those on certain medications like antibiotics or with conditions affecting participation are excluded.

Inclusion Criteria

I am 18 years old or older.

Any person of child-bearing potential, must have a negative beta-HCG test and must agree to use an adequate form of birth control throughout the clinical trial.

I have had a hole in my eardrum for at least 6 months.

Exclusion Criteria

Active alcohol or drug abuse within 6 months prior to study entry

My tissue damage is due to a burn or radiation therapy.

Subjects having any granulation or soft tissue density due to inflammation, or infection in mastoid antrum determined by CT scanning (Temporal bone CT scanning)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Treatment

Participants are randomized to receive FGF-2 or placebo treatment up to 3 treatments

Up to 134 days

Unblinded Crossover

Participants who failed placebo treatments crossover to receive unblinded FGF-2 for up to 3 treatments

Up to 134 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• FGF-2
• Placebo

Trial Overview The trial is testing FGF-2's ability to heal long-term tympanic membrane (ear drum) perforations versus a placebo. It's double-blinded: neither doctors nor patients know who gets real treatment. If the placebo fails after three tries, those patients get FGF-2 in an unblinded crossover phase.

Participant Groups

Group I: Human Fibroblast Growth Factor-2 (FGF-2) Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

The application of basic fibroblast growth factor (bFGF) significantly improves the closure rate of tympanic membrane (TM) perforations, with an odds ratio of 7.33 based on a meta-analysis of 14 studies involving 1,072 participants.

While bFGF treatment accelerates healing time for TM perforations, it does not show a significant impact on improving hearing, indicating its primary benefit is in promoting tissue repair rather than auditory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis. Huang, J., Teh, BM., Eikelboom, RH., et al.[2022]

In a phase 2 clinical trial involving 54 patients with chronic tympanic membrane perforations, fibroblast growth factor-2 (FGF-2) treatment did not show a statistically significant improvement in closure rates compared to a placebo, with closure rates of 57.5% for FGF-2 and 71.4% for placebo.

There were no significant differences in hearing outcomes between the FGF-2 and placebo groups, indicating that FGF-2 may not be an effective treatment for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical fibroblast growth factor-2 for treatment of chronic tympanic membrane perforations. Santos, F., Shu, E., Lee, DJ., et al.[2022]

In a study of 147 patients with traumatic tympanic membrane perforations, treatment with basic fibroblast growth factor (bFGF) resulted in a high healing rate of 98.0%, regardless of the timing of treatment within the first four weeks after injury.

The average healing times for small perforations were significantly shorter when treated within 8 to 14 days after injury, indicating that bFGF is an effective treatment option for tympanic membrane injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the effectiveness of basic fibroblast growth factor treatment on traumatic perforation of the tympanic membrane at different time points. Lou, Z., Tang, Y., Wu, X.[2013]

In a study of 86 patients with large traumatic tympanic membrane perforations, both epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) significantly improved closure rates compared to an observation-only group, with closure rates of 86.2% and 89.3% respectively versus 72.4% for observation.

The average time for closure was significantly shorter in the EGF and bFGF groups compared to the observation group, indicating that these growth factors can accelerate healing, although there was no significant difference in effectiveness between EGF and bFGF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study on the effects of EGF and bFGF on the healing of human large traumatic perforations of the tympanic membrane. Zhengcai-Lou, ., Zihan-Lou, ., Yongmei-Tang, .[2016]

In a mouse model of chronic tympanic membrane perforations, heparin binding epidermal growth factor-like growth factor (HB-EGF) demonstrated a significantly higher healing rate (83.3%) compared to fibroblast growth factor 2 (FGF2, 31.6%) and epidermal growth factor (EGF, 15.8%).

The study suggests that HB-EGF not only promotes better healing but also results in tympanic membranes that resemble normal structure, indicating its potential as an effective nonsurgical treatment option for chronic TM perforations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model. Santa Maria, PL., Weierich, K., Kim, S., et al.[2018]

Topical application of 400 ng of fibroblast growth factor (FGF) significantly accelerated the healing of tympanic membrane perforations in rats, reducing the closure time from 8.8 days in untreated ears to 6.1 days.

Higher doses of FGF led to complications such as myringitis, while a dose of 200 ng did not show any significant difference compared to the placebo, indicating that the optimal dose for healing is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibroblast growth factor improves the healing of experimental tympanic membrane perforations. Mondain, M., Saffiedine, S., Uziel, A.[2019]

Fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF) both demonstrated effective closure rates for tympanic membrane (TM) regeneration, with FGF2 showing closure rates of 55%-100% for acute perforations compared to 10%-62.5% in controls, while EGF showed 30.3%-100% for chronic perforations.

EGF was found to be more effective for acute TM perforations, whereas FGF2, especially when combined with biological scaffolds, was superior for chronic perforations, although it had higher rates of reperforation over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGF2 and EGF for the Regeneration of Tympanic Membrane: A Systematic Review. Lou, Z., Lou, Z., Jiang, Y., et al.[2022]

Fibroblast growth factor-2 has shown a high success rate (89.3-100%) in regenerating tympanic membrane perforations in humans, with an average closure time of about 2 weeks, indicating its efficacy in treating both acute and chronic cases.

When combined with Gelfoam, fibroblast growth factor-2 achieved an impressive success rate of 83-98.1% for chronic perforations, compared to only 10% for those treated with gelatine sponge alone, highlighting its potential advantages over traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regeneration of the tympanic membrane using fibroblast growth factor-2. Lou, ZC., Lou, ZH., Xiao, J.[2018]

In a study of 138 patients with traumatic tympanic membrane perforations, the use of fibroblast growth factor-2 (FGF-2) delivered via Gelfoam patches resulted in a significantly higher closure rate of 97.9% compared to 70.7% in the observation group.

FGF-2 plus Gelfoam patches not only improved closure rates but also reduced closure times to an average of 15.7 days, making it a promising minimally invasive treatment option for tympanic membrane perforations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fibroblast growth factor-2 delivered via a Gelfoam patch on the regeneration of myringosclerotic traumatic eardrum perforations lying close to the malleus. Jin, ZH., Dong, YH., Lou, ZH.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Topical fibroblast growth factor-2 for treatment of chronic tympanic membrane perforations. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Analysis of the effectiveness of basic fibroblast growth factor treatment on traumatic perforation of the tympanic membrane at different time points. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Comparative study on the effects of EGF and bFGF on the healing of human large traumatic perforations of the tympanic membrane. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Fibroblast growth factor improves the healing of experimental tympanic membrane perforations. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

FGF2 and EGF for the Regeneration of Tympanic Membrane: A Systematic Review. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Regeneration of the tympanic membrane using fibroblast growth factor-2. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

The effects of fibroblast growth factor-2 delivered via a Gelfoam patch on the regeneration of myringosclerotic traumatic eardrum perforations lying close to the malleus. [2018]